Recently, some synthetic nitrogen-based heterocyclic molecules, such as PJ34, have shown pronounced antitumor activity. Therefore, we designed and synthesized new derivatives characterized by a nitrogen-containing scaffold and evaluated their antiproliferative properties in tumor cells. We herein report the effects of three newly synthesized compounds on cell lines from three different human cancers: triple-negative breast cancer, colon carcinoma and glioblastoma. We found that two of these compounds did not affect proliferation, while the third significantly inhibited replication of the three cell lines. Moreover, this third molecule at 20 μM led to the upregulation of p21 and p27 and blockage of the cell cycle at G0/G1; in addition, it induced apoptosis in all three cell lines when used at higher concentrations (30-50 μM). The results demonstrate that this compound is a potent inhibitor of replication, an inducer of apoptosis and a negative regulator of cell cycle progression for cancer cells of different histotypes. Our data suggest a potential role for this new molecule as an interesting and powerful tool for new approaches in treating various cancers.

Discovery of a pyrimidine compound endowed with antitumor activity / Taglieri, Ludovica; Saccoliti, Francesco; Nicolai, Alice; Peruzzi, Giovanna; Madia, Valentina Noemi; Tudino, Valeria; Messore, Antonella; Di Santo, Roberto; Artico, Marco; Taurone, Samanta; Salvati, Maurizio; Costi, Roberta; Scarpa, Susanna. - In: INVESTIGATIONAL NEW DRUGS. - ISSN 0167-6997. - 38:1(2020), pp. 39-49. [10.1007/s10637-019-00762-y]

Discovery of a pyrimidine compound endowed with antitumor activity

Taglieri, Ludovica
Primo
;
Saccoliti, Francesco
Secondo
;
NICOLAI, ALICE;Peruzzi, Giovanna;Madia, Valentina Noemi;Tudino, Valeria;Messore, Antonella;Di Santo, Roberto;Artico, Marco;Taurone, Samanta;Salvati, Maurizio;Costi, Roberta
Penultimo
;
Scarpa, Susanna
Ultimo
2020

Abstract

Recently, some synthetic nitrogen-based heterocyclic molecules, such as PJ34, have shown pronounced antitumor activity. Therefore, we designed and synthesized new derivatives characterized by a nitrogen-containing scaffold and evaluated their antiproliferative properties in tumor cells. We herein report the effects of three newly synthesized compounds on cell lines from three different human cancers: triple-negative breast cancer, colon carcinoma and glioblastoma. We found that two of these compounds did not affect proliferation, while the third significantly inhibited replication of the three cell lines. Moreover, this third molecule at 20 μM led to the upregulation of p21 and p27 and blockage of the cell cycle at G0/G1; in addition, it induced apoptosis in all three cell lines when used at higher concentrations (30-50 μM). The results demonstrate that this compound is a potent inhibitor of replication, an inducer of apoptosis and a negative regulator of cell cycle progression for cancer cells of different histotypes. Our data suggest a potential role for this new molecule as an interesting and powerful tool for new approaches in treating various cancers.
2020
breast cancer; colon carcinoma; glioblastoma multiforme; PJ34; phenathridinone; pyrimidine
01 Pubblicazione su rivista::01a Articolo in rivista
Discovery of a pyrimidine compound endowed with antitumor activity / Taglieri, Ludovica; Saccoliti, Francesco; Nicolai, Alice; Peruzzi, Giovanna; Madia, Valentina Noemi; Tudino, Valeria; Messore, Antonella; Di Santo, Roberto; Artico, Marco; Taurone, Samanta; Salvati, Maurizio; Costi, Roberta; Scarpa, Susanna. - In: INVESTIGATIONAL NEW DRUGS. - ISSN 0167-6997. - 38:1(2020), pp. 39-49. [10.1007/s10637-019-00762-y]
File allegati a questo prodotto
File Dimensione Formato  
Taglieri_Discovery_2019.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.52 MB
Formato Adobe PDF
1.52 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1274892
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 11
social impact